DESCRIPTION: RNA structure is important in understanding many biological processes, including translation regulation in messenger RNA, replication of single stranded RNA viruses and the function of structural RNAs and RNA/protein complexes. Modeling RNA secondary structure is sufficient for understanding RNA function in some situations. When greater detail is required, a secondary structure is a significant step towards a three dimensional model. The long term goal of this work is to develop the best possible algorithms for predicting RNA secondary structure by free energy minimization using the most up-to-date thermodynamic parameters available. In this project, non-canonical base pairs will be permitted, and the prediction of multi-branched loops will be improved by including coaxial stacking interactions of adjacent helices. Statistical rules for RNA folding will be derived from large databases of ribosomal RNA (rRNA) secondary structures by computing log-likelihood statistics for base pair stacking interactions. These numbers can be regarded as "pseudo energy rules" for folding and should prove especially useful in assigning weights when non-standard base pairs occur. Statistics on interior loop size and asymmetry should prove similarly useful in developing rules for RNA folding that supplement thermodynamic measurements. Suboptima folding will be computed to mitigate the uncertainties in the modeling and to reflect the biological reality that alternative folding can exist. This suboptimal approach will be melded for the first time with a partition function calculation that will allow the computation of probabilities of base pair formation. Reliability of the algorithms will be tested by folding rRNAs of known secondary structure. One important application of RNA secondary structure prediction is to the modeling of single stranded RNA viruses. It is proposed to extend computer modeling on the RNA coliphage, Q3, to structure predictions on a variety of deletion mutants. Some of these mutants are non-viable and a minority of these recover some activity by enlarging the deletion. It is an aim of this proposal to correlate predicted structural plasticity of these coliphage mutants with their observed activity.